Dental caries, a multifactorial complex disease, remains the one of the most common chronic disease of human beings. The etiology of dental caries has been studied extensively, and both environmental and genetic factors have been implicated in caries risk. Our long-term goal is to improve understanding of the mechanism leading to dental caries development in both children and adults by uncovering underlying genetic risk factors that alone or through interaction with environmental factors, increase caries risk, thus informing new strategies for prevention and treatment. The objective of this application, which is the next step in pursuit of that goal, is to develop and test new approaches for modeling dental caries in genetic epidemiology studies, and then to apply those approaches to better understand the interaction between genetic and environmental risk factors using a large existing genome-wide dataset.
In Aim 1 we will study epidemiological properties, heritabilities, and modeling strategies for various caries phenotypes, and in Aim 2 we will look at the power of different gene x environment modeling strategies in the context of whole-genome scanning. The successful completion of Aims 1 and 2 will provide critical statistical and epidemiological tools for current and future studies of the genetic epidemiology of dental caries.
In Aim 3 we will apply the best approaches from Aims 1 and 2 to several existing GWAS caries datasets to identify and understand genetic and environmental risk factors that affect caries risk. The successful completion of Aim 3 will lead to new discoveries about the etiology of caries, and in particular about the gene x environment interactions that differentially affect risk in primary, permanent, and mixed dentition. This better understanding will eventually lead to better prevention and treatment.

Public Health Relevance

Dental caries, a multifactorial complex disease, remains the one of the most common chronic diseases of human beings. We propose to compare and evaluate a variety of caries modeling strategies for identifying genetic and environmental risk factors and their interactions. The successful completion of this project will eventually lead to better understanding of the etiology, prevention and even the customized treatment strategies of caries.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Small Research Grants (R03)
Project #
5R03DE021425-02
Application #
8245722
Study Section
Special Emphasis Panel (ZDE1-MH (23))
Program Officer
Harris, Emily L
Project Start
2011-04-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2012
Total Cost
$227,250
Indirect Cost
$77,250
Name
University of Pittsburgh
Department
Dentistry
Type
Schools of Dentistry
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Zeng, Z; Feingold, E; Wang, X et al. (2014) Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries. Caries Res 48:330-8
Shaffer, J R; Feingold, E; Wang, X et al. (2013) Clustering tooth surfaces into biologically informative caries outcomes. J Dent Res 92:32-7
Shaffer, J R; Feingold, E; Wang, X et al. (2013) GWAS of dental caries patterns in the permanent dentition. J Dent Res 92:38-44
Zeng, Z; Shaffer, J R; Wang, X et al. (2013) Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition. J Dent Res 92:432-7
Shaffer, John R; Feingold, Eleanor; Wang, Xiaojing et al. (2012) Heritable patterns of tooth decay in the permanent dentition: principal components and factor analyses. BMC Oral Health 12:7
Shaffer, J R; Wang, X; Desensi, R S et al. (2012) Genetic susceptibility to dental caries on pit and fissure and smooth surfaces. Caries Res 46:38-46
Wang, X; Willing, M C; Marazita, M L et al. (2012) Genetic and environmental factors associated with dental caries in children: the Iowa Fluoride Study. Caries Res 46:177-84
Larjava, H; Koivisto, L; Hakkinen, L et al. (2011) Epithelial integrins with special reference to oral epithelia. J Dent Res 90:1367-76
Shaffer, J R; Wang, X; Feingold, E et al. (2011) Genome-wide association scan for childhood caries implicates novel genes. J Dent Res 90:1457-62